Revisiting synthetic lethality of Gcn5-related N-acetyltransferase (GNAT) family mutations in Haloferax volcanii

bioRxiv [Preprint]. 2025 Feb 17:2025.02.13.638158. doi: 10.1101/2025.02.13.638158.

Abstract

Lysine acetylation is a post-translational modification that occurs in all domains of life, highlighting its evolutionary significance. Previous genome comparison identified three Gcn5-related N-acetyltransferase (GNAT) family members as lysine acetyltransferase homologs (Pat1, Pat2, and Elp3) and two deacetylase homologs (Sir2 and HdaI) in the halophilic archaeon Haloferax volcanii, with elp3 and pat2 proposed as a synthetic lethal gene pair. Here we advance these findings by performing single and double mutagenesis of elp3 with the pat1 and pat2 lysine acetyltransferase gene homologs. Genome sequencing and PCR screens of these strains reveal successful generation of Δelp3, Δpat1Δelp3, and Δpat2Δelp3 mutant strains. Although these mutant strains exhibited a reduced growth rate compared to the parent, they remained viable. Overall, this study provides genetic evidence that elp3 and pat2, while impacting cell growth, are not a synthetic lethal gene pair as previously reported.

Keywords: Haloferax volcanii; archaea; lysine acetyltransferase; mutant generation; post-translational modification.

Publication types

  • Preprint